1. Field Of The Invention
(S)3-Hydroxy-3-methylglutaryl coenzyme A ((S)HMG-CoA) is a substrate in many known biological reactions, including the production of 3-methyl glutaconyl coenzyme A, acetyl coenzyme A, and mevalonate. The last reaction is the most studied and is catalyzed by the enzyme HMG-CoA reductase (EC 1.1.1.34). Mevalonate is the unique precursor for the synthesis of isoprenoids, including sterols, sex hormones, pheromones, carotenoids, rubber, and the like. The availability of large amounts of biologically active (S)HMG-CoA is desirable for the study of these biologically important reactions.
Heretofore, commercial sources for HMG-CoA have relied on a chemical synthesis utilizing 3-hydroxy-3-methylglutaryl anhydride and coenzyme A which yields a racemic mixture of the biologically-active (S) isomer and the biologically-inactive (R) isomer. Such mixtures, at best, yield only one-half the biological activity of pure (S)HMG-CoA. Moreover, it has been found by the inventors herein that the (R) isomer is a competitive inhibitor of the (S) isomer in the conversion of the (S) isomer to mevalonate. Thus, it would be highly desirable to provide an efficient, economic synthesis for (S)HMG-CoA which results in a product free of the (R) isomer.
2. Description of the Prior Art
Henning, et al. (1959) Arch. Biochem. Biophys., 83:259, describe a two-step synthesis of (S)HMG-CoA which uses partially purified enzymes from sheep liver and bacteria.